Scandinavian Journal of Gastroenterology · 2002 · 39 citations · 24 references
Life SciencesGeneticsImmunologyAutoimmunityHuman GeneticsImmunogeneticsAutoimmune Disease Susceptibility GenesAutoimmune DiseasesCeliac DiseaseDisease Susceptibility LociGenetic Susceptibility To AutoimmunityMajor Histocompatibility ComplexCeliac Disease ImmunogeneticsHla Allele PolymorphismHla AllelesHla Genotype AssociationsHla Polymorphism AnalysisHla Risk AllelesLinkage Disequilibrium AnalysisTransmission Disequilibrium Test
BACKGROUND: A genetic susceptibility to coeliac disease is well established, involving HLA and non-HLA components. CTLA4 is an important regulator of T-cell function and some studies have suggested that sequence variation in the gene might be a determinant of disease susceptibility, although the evidence is conflicting. METHODS: Sixty-two children with biopsy-proven coeliac disease attending a single centre in Sweden were studied. All were genotyped for presence of the HLA-DQA1*0501, B 1*0201 alleles. Those who carried the HLA-DQ heterodimer (58/62) were genotyped for the +49 (A/G) exon I polymorphism. The transmission disequilibrium test (TDT) was used to test for association between coeliac disease and the A allele. The entire CTLA4 gene was screened for other sequence variants using a combination of conformation-sensitive gel electrophoresis and direct sequencing. RESULTS: A significant association between the exon I polymorphism and coeliac disease was observed (P = 0.02). No other sequence variants in CTLA4 were detected. CONCLUSIONS: This study provides further evidence that variation in CTLA4 is a determinant of coeliac disease susceptibility. If not mediated through the +49 (A/G) dimorphism directly, then the effect is likely to be mediated through linkage disequilibrium.
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Arupa Ganguly, Matthew J. Rock, Darwin J. Prockop · Proceedings of the National Academy of Sciences · 1993 · 677 citations